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Eur J Cardiothorac Surg 1998;14:27-32
© 1998 Elsevier Science NL

Lung volume reduction or lung transplantation for end-stage pulmonary emphysema?¹

Division of Cardiothoracic Surgery, University of Pittsburgh Medical Center, 200 Lothrop Street Suite C-700, Pittsburgh, PA 15213, USA

Received 29 September 1997; received in revised form 9 March 1998; accepted 15 April 1998.

Corresponding author. Tel.: +1 412 648 9135; fax: +1 412 648 1029; e–mail: internet:zenati@pittsurg.nb.upmc.edu

	Abstract

Top Abstract Introduction Patients and methods Results Discussion Appendix A. Conference... References

 
Objective: As the waiting period for lung transplant (LT) candidates with end-stage pulmonary emphysema (COPD) continues to increase, there is a need for alternative treatments to reduce the morbidity and mortality associated with COPD. We hypothesized that lung reduction (LR) may avoid the need for subsequent LT in patients on the waiting list that are also candidates for LR. Methods: From July 1994 to December 1995, 20 patients received LR as alternative to LT. The average age was 58±7 years; 11 were males. Eighteen patients had primary COPD and two had alpha-1 antitrypsin deficiency. Eighteen LRs were thoracoscopic (two bilateral and 16 unilateral) and two were done through a median sternotomy. Results: At a follow-up of 32±4 months, 19 patients are alive (19/20=95%). Fifteen patients (15/20=75%) are currently off the LT list and doing well: FEV1 is 40±18% predicted at 2 years compared with 22.7±6% before LR (P<0.001); FVC is 84±13% at 2 years compared with 55±7% (P<0.001) and the RV is 145±59% compared with 270±58% (P<0.001). One patient (5%) required extra-corporeal membrane oxygenation (ECMO) after LR to the contralateral side of the first procedure and subsequently died. Two patients (10%) are currently listed for LT because of persistent symptoms. One patient (5%) in whom deterioration was secondary to exposure to toxic fumes, underwent successful LT. One patient (5%) is doing well from the pulmonary standpoint but is being worked up for new severe coronary artery disease (CAD). The freedom from LT is 95% (19/20) and the freedom from repeat LR is 85% (17/20). Conclusions: LR has the potential to offer an effective palliative alternative to LT in 75% of selected patients up to 32 months of follow-up. Widespread use of bilateral LR is anticipated to further improve the results.

Key Words: Lung reduction • Lung transplantation • Pulmonary emphysema

	Introduction

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Lung transplantation (LT) has undergone significant evolution in the last 15 years, including the process of patient selection. This process weights the risks and benefits of transplant surgery for each candidate, attempts to maximize outcome of the lung allograft and patient, identifies the best surgical procedure for an individual patients clinical situation and disease, and functions to assure the best use of a limited resource [1]. For patients with end-stage lung disease secondary to emphysema (COPD), Lung reduction (LR) surgery has been proposed as a therapeutic option as bridge [2] or alternative to LT [3] [4].

Both LT and LR are evolving therapies, and the best option for the individual patient with COPD remains to be determined. One year survival after LT for COPD is 78% and 3 year survival is 60% [5]. There are no long-term survival data regarding LR and the best surgical technique and the relative role of pulmonary rehabilitation alone are still debated. We have previously reported preliminary results with LR in LT candidates [3]. The hypothesis that we wanted to test in the present study was that LR performed as an alternative to LT could avoid the need for subsequent LT over an intermediate term follow-up.

	Patients and methods

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From July 1994 to December 1995, 20 LT candidates received LR as alternative therapy as part of a prospective study. The average age was 58±7 years. There were 11 males. Eighteen patients had primary COPD and two had alpha-1 anti-trypsin deficiency. All of these patients had severely impaired quality of life despite maximal medical therapy and disabling dyspnea at less than 50 yards of walking. Eight patients (40%) had PaCO₂>45 Torr. The baseline dyspnea index was 0.9.

All patients underwent routine work-up for LT. Selection criteria for LT (Table 1) and our evaluation protocol were previously published [3].

The nuclear medicine evaluation includes ventilation and perfusion lung scanning. Ventilation imaging is performed with 10–20 mCi of ¹³³Xe. After planar imaging, single photon emission CT (SPECT) perfusion imaging is performed using a dual head gamma camera (BIAD, Trionix, Twinsburg, OH) with high resolution collimators. The nuclear images are used to determine the side which has the worst ventilation and perfusion and to aid in determining the areas of lung to be resected.

The daily experience with dyspnea is measured by use of the baseline dyspnea index (BDI). A health care provider selects from one to five grades of dyspnea based on a brief history. In addition, patients were also categorized using the modified Borg scale that uses a subjective perspective to assess the extent of activity necessary to cause dyspnea; the higher the score, the worse the breathlessness.

Exclusion criteria for LR (Table 2) included known pulmonary hypertension (systolic pulmonary artery pressure >55 Torr), history of smoking tobacco within the last 3 months, morbid obesity (>1.5 lean body weight), unstable coronary artery disease, end-stage cancer, non-ambulatory and ventilator-dependent patients. Patients that had previously undergone open thoracic surgical procedures on the side designated for unilateral LR were also excluded. Patients whose disease was characterized by large bullae with compressive signs on chest CT were excluded from the study. Patients were seen in consultation by the nutrition service for assessment of nutritional status. Patients taking >20 mg of prednisone per day were not eligible for surgery until they were weaned below this level. Participation in a cardiopulmonary rehabilitation program was not required for inclusion in the study. Selection of patients was performed by a multidisciplinary team including thoracic surgeons, pulmonologists, radiologists and transplant coordinators.

After surgery, pulmonary function, diagnostic imaging and the 6MW were repeated to evaluate the extent of improvement. Change in the degree of functional impairment after surgery was determined using a transitional dyspnea index (TDI). This index measures the change from baseline in three categories: functional impairment, the magnitude of the task needed to evoke dyspnea and the magnitude of the effort needed to evoke dyspnea. Scoring ranged from -9 (major deterioration) to +9 (major improvement).

All patients included in this study fulfilled both inclusion criteria for LR and LT (Table 3). The protocol for this study was approved by the Biomedical Institutional Review Board of the University of Pittsburgh and all patients gave written informed consent

Airway intubation was performed using a left-sided double lumen endotracheal tube. Pulse oxymetry and end-tidal carbon dioxide monitoring was followed throughout the case.

LR was performed upon the side most severely affected by the emphysematous process; in particular, the density mask images of the CT scan highlighted the areas of worst anatomic disease as well as zones of more normal lung, while the SPECT perfusion study demonstrated zones of significant hypoperfusion. These areas were focused upon during the resection especially when the ventilation studies had shown washout abnormalities. When both lungs demonstrated an equal degree of parenchymal destruction, a bilateral approach was used with sequential thoracoscopic LR or bilateral LR through a median sternotomy.

Unilateral thoracoscopic LR was performed with the patient in lateral decubitus position. In the majority of cases, three to five ports were used for access. The thoracoscope was introduced into the chest through the 7th or 8th intercostal space at the mid to posterior axillary line. In six patients (6/20=30%), a combination of endostapler resection (for about 90% of the total volume reduction) together with sparing use of Nd:YAG laser was used. Laser was employed mainly in areas of diffuse bollous formation near the pulmonary hilum or located at angles difficult to reach with the endostapler. Endostapler resection was the preferred method of LR in 12 patients (20/35=57%): according to the extent of the area to be resected we used either a 30-mm (US Surgical Corp, Norwalk, CT) or a 60-mm (Ethicon Endo-Surgery, Cincinnati, OH) stapler. The staple line was buttressed with bovine pericardium.

The goal of LR was to reduce the volume of the lung by 25%. The extent of resection was dictated by the preoperative perfusion studies. Strips of lung tissue were resected along the edges of each lobe such as along the fissures or anteriorly and posteriorly to the apex of the upper lobe and along the basal segments or superior segment of the lower lobe. Lung was periodically inflated during the procedure to evaluate the extent of resection accomplished in each lobe of the lung so as to avoid over-resection. Staple lines were buttressed with bovine pericardium. At the end of the procedure three chest tubes were placed into the pleural cavity through the intercostal access ports used during the procedure. No pleural abrasion or pleurectomy was performed. Lungs were re-expanded and ventilation was re-established aiming to keep peak airway pressure at the minimum required to achieve an adequate tidal volume (<30 mmHg). Chest tubes were placed on -10 cmH₂0 of water suction in the operating room and adjusted thereafter.

Statistical analysis
Data were expressed as mean±standard deviation (SD). Continuous variables were compared as group means. Preoperative values were compared with postoperative values at each of several time points using a Student's t-test. The variables were near normally distributed. Independent comparisons were made at each time points. A P value <0.05 was considered statistically significant.

	Results

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Survival
All patients survived LR and 19 patients are currently alive (19/20=95%) at a follow-up of 32±4 months. One patient (5%) became septic after a repeat LR to the contralateral side of the first procedure, performed 14 months before; he required extra-corporeal membrane oxygenation (ECMO) and subsequently died.

LR orocedural outcomes
Sixteen patients (16/20=80%) underwent unilateral thoracoscopic LR (six combined laser and staple, ten staple only). Two patients (2/20=10%) received bilateral thoracoscopic staple LR and two (2/20=10%) had bilateral staple sternotomy LR. The length of stay in hospital after LR was 20±12 days (range 9–48 days). The most common complication was prolonged (>5 days) airleak in 15 patients (15/20=75%). Other complications were: pneumonia in three (15%), ileus in two (10%), empyema in one (5%), reintubation in one (5%).

Functional results
Fifteen patients (15/20=75%) are currently off the LT list and doing well: the results at 6, 12, 18 and 24 months follow-up for these 15 patients are detailed in Table 4. At 2 years follow-up, maintenance of the statistically significant early functional improvement was observed for FEV1, FVC, RV, TLC, PaO₂ and borg dyspnea index. Up to 18 months follow-up, the 6MWD was significantly better than pre-LR. Two patients (10%) are currently listed for LT because of persistent symptoms and required repeat LR to the contralateral side to the first procedure. One patient (5%) in whom deterioration was secondary to exposure to toxic fumes, underwent successful LT 14 months following the original LR. One patient (5%) is doing well from the pulmonary standpoint but is being worked up for new severe CAD. Overall, the freedom from LT is 95% (19/20) and the freedom from repeat LR is 85% (17/20)

	Discussion

Top Abstract Introduction Patients and methods Results Discussion Appendix A. Conference... References

Lung transplantation is associated with long waiting period due to the limited number of available donor organs, averaging 18 months at our institution and carrying a 15% mortality. Given the prevalence of COPD in the general population, it is not surprising that it represents the most common indication for lung transplantation. Both single and double lung transplant have been advocated for COPD; despite the superior outcomes in FEV1 and other indices of pulmonary function after bilateral lung transplant, it confers only modest advantage over single lung transplant with respect to exercise tolerance. Perioperative mortality is about 10% and despite refinement in preservation techniques and better control of rejection, the results of LT are less the optimal: the 5 year survival is only 45%.

Lung reduction pioneered by Brantigan in the 1950s [7] recently emerged as a potential surgical option for the treatment of advanced emphysema resulting in improved pulmonary function, gas exchange, exercise tolerance and perceived dyspnea in some but not all patients who undergo the procedure [8]. The mechanism of action of lung reduction appears to be related to increased elastic recoil of the lung, restoration of negative intrathoracic pressure and decreased right ventricular pressure [9]. A decreased work of breathing resulting from reduction in airway resistance has also recently been demonstrated [10] after bilateral lung reduction. Long-term durability of early improvement following LR has not yet been demonstrated [11]. The results of lung reduction and lung transplantation have been compared in a non randomized fashion. The authors [4] reported an improvement in FEV1 of 79% for the LR group, 231% for the SLT group and 498% for the BLT group at 6 months follow-up. Exercise endurance measured by 6MWD increased 28% in the LR group, 47% in the SLT group and 79% in the BLT group. Overall mortality at 1 year was 3, 10.2 and 16% for the LR, SLT and BLT groups, respectively. LR also is much less expensive than lung transplantation ($US30 000–70 000 versus $US165 000 for the hospital cost only) [12].

The advantage of bilateral over unilateral lung reduction is established [13] [14] and has become our approach of choice since September 1995 [15]. Lung reduction has been shown to achieve significantly better 6MWD at 6 months compared with continued pulmonary rehabilitation alone [16]. Despite this evidence for effectiveness, Medicare, the largest third party payer of health care in the US, discontinued reimbursement to hospitals for LR in January 1996 for lack of adequate scientific proof of improvement. This has caused a sharp reduction in the number of the procedures being performed in the US. A prospective randomized controlled trial involving 18 selected centers will begin in the Fall of 1997 under the sponsorship of the Health Care Financing Corporation (the administrators of Medicare) and the National Institutes of Health.

In the present study, we have identified a small cohort of patients that were found to be good candidates for both lung reduction and lung transplantation; these patients received lung reduction and were followed to evaluate the potential for this form of therapy to be an alternative to lung transplantation. The rationale is that patients that undergo lung reduction as an alternative to lung transplantation may reduce the demand on the limited supply of donor organs leaving lungs available for patients with diseases for which lung transplantation is the only alternative. The significant early benefit of the procedure, that we have already reported [3], was confirmed at 2 years follow-up. At a follow-up of 32 months, 75% of patients are off the transplant list, the survival is 95%, the freedom from lung transplantation is 95% and the freedom from repeat lung reduction is 85%.

In conclusion, our results in a limited study, and using a variety of surgical techniques for lung reduction, supports continued evaluation of lung reduction as potential alternative to lung transplantation for selected patients with advanced emphysema.

	Footnotes

 
Presented at the 11th Annual Meeting of the European Association for Cardio-thoracic Surgery, Copenhagen, Denmark, September 28 – October 1, 1997.

	Appendix A. Conference discussion

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Dr W. Wedner (Zurich, Switzerland): Dr. Zenati, you presented results and improvement in the FEV1 from 22% predicted up to 40% predicted, which is an improvement in absolute values certainly much higher than 50%. This improvement is much better than most centers achieve with bilateral procedures, and it is much better than the results which were presented from your group, by Keenan, for unilateral procedures. Could you explain to us how you changed your program that you could improve your results so dramatically? And my second question is, you indicated patients up to the age of 65 years for lung transplantation, which is higher than in most centers. If you perform initially a volume reduction surgery and if they deteriorate after 1 or 2 years, they are 67 years. With your waiting time they get 70 years at the time of transplantation. How do you handle this problem?

Dr Zenati: Lung reduction, like lung transplantation, is very much in evolution. We have witnessed a tremendous improvement in selection criteria, surgical techniques, ability to handle air leaks, in the last 3 or 4 years. When we started in 1994, our approach of choice was unilateral lung reduction. But as we moved and we increased our experience, we were able to identify much better patients that were good candidates for lung reduction and anticipate better results. For instance, currently we have knowledge that the combination of a high PCO₂ greater than 45 and a predicted DLCO less than 25 is dismal. So we have been able to better select, as our experience increased, patients that were to have better results. And also we believe that bilateral lung reduction, like your group pretty much is advocating, is going to be the way to go. The results actually with bilateral are much better than this cohort, and groups an increase of 120% versus the baseline has been obtained.

Regarding age, this is a work-in-progress. Currently, lung reduction has as one of its advantages that it does not burn any bridges, so to speak, so you can go on and have lung transplantation without added morbidity. Regarding the age range, 65 years is basically the cut-off for lung transplantation. So right now our policy is that if the patient is approaching 65, and they are on the lung transplant list, we might try to actually give them a transplant so they don't eliminate this option in their future. But for younger patients, and this group is younger than the average for lung reduction, we think this is a good option. We don't know what are the long-term results, but I think Cooper's 2 years of follow-up and our follow-up results are encouraging. You have to keep in mind that this represents the early experience of our group. Now we do routinely bilateral lung reduction. We are much better able to identify patients that are going to do better. We know that upper lobe is going to have better results and heterogeneous disease is going to give better results overall.

Dr J. Benfield (Sacramento, CA, USA): The place for lung reduction surgery (LVRS) for the long run remains to be seen as you have indicated. Clearly when Joel Cooper presented his data initially at the AATS, he indicated that LVRS had been started for the purpose of bridging to transplantation. I thought it might be interesting for our colleagues in Europe to know something about what has happened with regard to lung reduction and the National Institutes of Health (NIH) and the Health Care Financing Agency (HCFA) in the US. When Joel Cooper presented his paper, there was a surge of interest in lung reduction. HCFA, however, decided that this was an experimental procedure for which it was not going to pay for any further. Fortunately, the Society of Thoracic Surgeon (STS) quite a few months before that, had decided that this procedure required a look by thoracic surgeons and pulmonologists. The STS initiated the process of developing a randomized, prospective protocol whereby the effect of lung reduction could be compared with the best available medical treatment.

This protocol ultimately was adopted, in somewhat modified form, by the HFCA, albeit the details are not yet available. It is the first time that these two groups came together. One group being an investigational agency, the NIH, and the other group being the HFCA that pays for medicare treatment in the US. There is now a forthcoming protocol in which some 18 centers in the US have been selected to evaluate LVRS as compared with the best available medical treatment. In my judgment, if aortocoronary bypass 25 or 20 years ago, had been subjected to the same kind of analysis, it would have proven itself to be as useful as it is much quicker and the cardiologists would not have delayed the acceptance of aortocoronary bypass for nearly as long they did.

Dr Zenati: We are going to be participating in the Fall of this year in this multicenter prospective trial. There is already some data from Cooper's institution, in St. Louis, regarding a prospective, randomized study comparing rehabilitation versus lung reduction. What they showed is that after 6 months there was equal improvement in both, but then beyond 6 months only lung reduction maintained advantage over rehabilitation. So we are biased, of course, that lung reduction is going to pan out as the best option. But it is very good that NIH and NHLBI are sponsoring these trials. It is going to be very, very important for the future of surgery for emphysema.

	References

Top Abstract Introduction Patients and methods Results Discussion Appendix A. Conference... References

 

1. Smith C.M. Patient selection, evaluation and preoperative management for lung transplant candidates. Clin Chest Med 1997;18:183-197.[Medline]
2. Zenati M., Keenan R.J., Landreneau R.J., Paradis I.L., Ferson P.F., Griffith B.P. Lung reduction as bridge to lung transplantation in pulmonary emphysema. Ann Thorac Surg 1995;59:1581-1583.[Abstract/Free Full Text]
3. Zenati M., Keenan R.J., Sciurba F.C., Manzetti J.D., Landreneau R.J., Griffith B.P. Role of lung reduction in lung transplant candidates with pulmonary emphysema. Ann Thorac Surg 1996;62:994-999.[Abstract/Free Full Text]
4. Gaissert H.A., Trulock E.P., Cooper J.D., Sundaresan R.S., Patterson G.A. Comparison of early functional results after volume reduction or lung transplantation for chronic obstructive pulmonary disease. J Thorac Cardiovasc Surg 1996;111:296-307.[Abstract/Free Full Text]
5. Hosenpud J.D., Bennett L.E., Keck B.M., Fiol B., Novick R.J. The registry of the International Society for Heart and Lung Transplantation: fourteenth official report – 1997. J Heart Lung Transplant 1997;16:691-712.[Medline]
6. Muller N.L., Staples C.A., Miller R.R., Abboud R.T. `Density mask': an objective method to quantitate emphysema using computed tomography. Chest 1988;94:782-787.[Abstract/Free Full Text]
7. Brantigan O.C., Mueller E. Surgical treatment of pulmonary emphysema. Am Surg 1957;23:789-794.[Medline]
8. Benditt J.O., Albert R.K. Surgical options for patients with advanced emphysema. Clin Chest Med 1997;18:577-593.[Medline]
9. Sciurba F.C., Rogers R.M., Keenan R.J., Slivka W.A., Gorcsan J., Ferson P.F., Holbert J.M., Brown M.L., Landreneau R.J. Improvement in pulmonary function and elastic recoil after lung-reduction surgery for diffuse emphysema. N Engl J Med 1996;334:1095-1099.[Abstract/Free Full Text]
10. Miller DA, Dowling RD, McConnell JW, Skolnick JL. Effects of lung volume reduction surgery on lung and chest wall mechanics. Program of the 32nd Annual Meeting of the Society of Thoracic Surgeons, January 29–31, 1996:96–97.
11. Sciurba F.C. Early and long-term functional outcomes following lung reduction surgery. Clin Chest Med 1997;18:259-276.[Medline]
12. Albert R.K., Lewis S., Wood D. Economic aspects of lung volume reduction surgery. Chest 1996;110:1068-1071.[Abstract/Free Full Text]
13. Stammberger U., Thurnheer R., Bloch K.E., Zollinger A., Schmid R.A., Russi E.W., Weder W. Thoracoscopic bilateral lung volume reduction for diffuse pulmonary emphysema. Eur J Cardio-thorac Surg 1997;11:1005-1010.[Abstract]
14. Cooper J.D., Trulok E.P., Triantafillou A.N. Bilateral pneumectomy (volume reduction) for chronic obstructive pulmonary disease. J Thorac Cardiovasc Surg 1995;109:106-119.[Abstract/Free Full Text]
15. Keenan RJ, Sciurba FC, Landreneau RJ. Superiority of bilateral versus unilateral thoracoscopic approaches to lung reduction surgery. Am J Respir Crit Care Med 1996;153(Suppl):A268.
16. Biggar D, Cooper JD, Patterson GA. Lung volume reduction surgery versus continued pulmonary rehabilitation alone in patients with COPD. Chest 1995;108:95S.

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Marco Zenati Robert J. Keenan Bartley P. Griffith Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zenati, M. Articles by Griffith, B. P. Search for Related Content PubMed PubMed Citation Articles by Zenati, M. Articles by Griffith, B. P.